Two interrelated areas are being investigated: 1. The origin of diversity of antibodies: a. The normal lambda 1 and lambda 2 murine light chains are being isolated from a large collection of independently derived hybridomas to establish the complete pattern of somatic variability of two unique germ-line v-genes. This study will also reveal any lambda polymorphic markers. b. The kappa anti-alpha-1,3 response has been shown to be determined by a v kappa-gene closely linked to the Ly 2,3 locus. Thus, response unlike the lambda 1 anti-alpha-1,3 kappa response evolves slowly following hyperimmunization and has all of the characteristics expected of a process of selection on somatic mutants. 2. The regulation of immune responsiveness. Many B-cell lines derived by fusion have been isolated and are being characterized for surface marker, Ig class, antibody specificity and functional behavior (inducibility and paralyzability). The inhibition of humoral responsiveness by T-cells is K/D restricted, a finding which has led us to a detailed dual recognition model of the T-cell receptor and the ontogeny of its expression. The test of this model is under analysis. The cooperating and inhibitory transmitters which regulate responsiveness of antigen sensitive cells are under isolation using a microculture assay which determines the number of induced antigen-sensitive cells as well as the clone size.